Method for nasal irrigation and drug delivery

ABSTRACT

A method of treating neoplasms of the nasal cavity. Fluid containing corticosteroids held in a canister is atomized via a compressed air supply to create particles sized for penetration and retention in the nasal cavity under pressure that is able to stent open the soft tissues of the nose to deliver the resultant mist into the whole of the nasal passages without the need for the patient to create an airstream through inhalation. The device consists of a main canister with a reservoir to hold the fluid, two air outlets and an insert that is placed over the air outlets, the insert having at least one outlet that is larger than the holes in the air outlet and allows the fluid to be atomized and injected directly into the nasal cavity.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application in a Continuation In Part and claims the benefit of andpriority to U.S. patent application Ser. No. 12/633,269 filed Dec. 8,2009, the technical disclosures of which are hereby incorporated hereinby reference.

TECHNICAL FIELD

The present invention relates to the delivery of fluid to the upperairway in mist or droplet form, either for the irrigation of the nasalpassages or the delivery of medication.

BACKGROUND OF THE INVENTION

The treatment of benign neoplasms of the nasal cavity, such as, e.g.,inflammatory nasal polyps, granulomas, etc., typically involves surgery,systemic doses of steroids, steroid injections and steroid irrigation.To date, these treatments have been costly and impractical for long termprevention or regrowth of the neoplasm.

Surgery presents risk to the patient and is expensive for both thepatient and the healthcare system, particularly regular, repeat surgicalprocedures common for these disorders. In addition, surgical resectionof both benign and malignant neoplasms and therapeutic surgicalalteration of the nose and paranasal sinuses often result in removal ofanatomic structures such as the nasal turbinates, nasal septum, nasalmucosa, etc. Such ablative and reconstructive surgeries can result indisruption of the natural filtering and humidification provided by thesestructures resulting in dryness, bleeding, crusting, increased risk ofinfection and changes in olfaction including hyposmia, dysosmia,parosmia and anosmia.

Current management includes saline irrigation and nasal sprays whichfrequently do not reach many of the areas of concern in the nasalvestibule and paranasal sinus areas. Such irrigation and nasal sprayscan also result in pooling of moisture that provides a nidus forinfection and can cause excessive irrigation that removes theimmunologic mucus blanket of the nose that serves as the body's naturaldefense from antigens and pathogens.

Systemic steroid dosing has its own risks, and injection therapyrequires frequent visits to the physician to obtain adequate dosing.High volume nasal rinses have been shown to be ineffective for deliveryof drugs. Metered dose inhalers do not deliver enough drug nor do theydeliver the drug to the right location, with data showing that 90% ofthe material reaches only the antrum or front third of the nasal cavity.

Devices used for administering liquid medication to a patient by way ofmist or liquid droplets are generally called nebulizers. Typical priorart nebulizers are designed with a single exist port whereby mist orliquid droplets exit the device to be inhaled by the patient. The mistfrom these nebulizers leaves the device in a low pressure flow rate as aresult of baffles or air dams that redirect a venturi jet stream ofliquid droplets as the liquid medication is drawn from a liquidreservoir in the device. These devices are best suited for theinhalation of the liquid droplets through the patient's mouth. However,medical conditions such as benign nasal neoplasms require theintroduction of liquid droplets through the patient's nasal passages.

Current nebulizers, with a single orifice and typically low pressureflow rates, are not effective for introducing liquid medication throughthe two nostrils of a patient, particularly when the patient's nasalpassages are congested or otherwise obstructed. In addition, currentnebulizers are designed primarily to deliver particles to the lowerairways and require considerable interaction from the patient, includinglong delivery times.

Therefore, it would be desirable to have a method for quickly deliveringdroplets or mists with an air stream and particle size designed to stayin the upper airway and reach the whole of the nasal mucosa for purposesof nasal irrigation and drug delivery.

SUMMARY OF THE INVENTION

The present invention provides a method of treating neoplasms of thenasal cavity. Fluid containing corticosteroids held in a canister isatomized via a compressed air supply to create particles sized forpenetration and retention in the nasal cavity under pressure that isable to stent open the soft tissues of the nose to deliver the resultantmist into the whole of the nasal passages without the need for thepatient to create an airstream through inhalation. The device consistsof a main canister with a reservoir to hold the fluid, two air outletsand an insert that is placed over the air outlets, the insert having atleast one outlet that is larger than the holes in the air outlet andallows the fluid to be atomized and injected directly into the nasalcavity. In one embodiment of the invention, antibiotics are included inthe fluid and administered concurrently with the corticosteroids toreduce steroid resistance of nasal polyps caused by bacterial infection.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features believed characteristic of the invention are setforth in the appended claims. The invention itself, however, as well asmode of use and advantages thereof, will best be understood by referenceto the following detailed description of illustrative embodiments whenread in conjunction with the accompanying drawings, wherein:

FIG. 1 is an exploded view of a nasal nebulizer in accordance with anembodiment of the present invention;

FIG. 2 shows a cross section view of the canister in accordance with analternate embodiment of the invention;

FIG. 3 shows an alternate embodiment of the cover in accordance with thepresent invention; and

FIG. 4 illustrates the use of the nasal nebulizer in accordance with thepresent invention.

DETAILED DESCRIPTION OF THE DRAWINGS

The present invention improves upon current nebulizer designs andprovides a method of delivering fluid to the nasal passages with littleinteraction required by the user, under sufficient pressure to stentopen the airway, and with particles of a size to ensure that themajority of the mist is retained or deposited within the upper airway.The invention also provides a nasal nebulizer designed to deliver a mistto the upper airway through both nostrils simultaneously.

FIG. 1 is an exploded view of a nasal nebulizer in accordance with anembodiment of the present invention. The nasal irrigation devicecomprises three major sections. The first major section is the maincanister 22 which has an expanded reservoir 10 that is capable ofholding up to 50 ml of fluid. The inner portion of the reservoir shapedat the bottom to ensure maximal uptake of fluid to reduce waste.

The main canister 22 also includes an air chamber 11 terminating in twoair exits 12 (one for each nostril) with holes sufficient to deliver anairstream that is able to atomize fluid and stent open the upper airway.In one embodiment, each exit port 12 has at least one hole of between0.020″ and 0.060″ (0.508 mm-1.524 mm) in diameter and a web-thickness ofbetween 0.030″ and 0.060″ (0.762 mm-1.524 mm).

On the bottom of the main canister 22 is a foot section 9 that includesone or more feet for stability and an air inlet 8 for the admission ofpressurized air to create the air stream through air exits 12. The footsection 9 enables the canister 22 to stand up when set on a horizontalsurface and is designed to fit into a standard docking port of an aircompressor pump to enable the device to remain upright in a hands-freemanner so as to remain filled with the air supply tube attached.

In the shown example, the main canister 22 has a two step diameter tofit a holder (not shown) and provide adequate fluid volume for nasalirrigation, with the smaller diameter foot section 9 enabling the userto rest device in the holder with tube attached. In an alternateembodiment (not shown) the foot section 9 is wider than the reservoirsection 10.

The second major section of the nebulizer is the insert 23, which isshown with a base 13 that holds the insert just off of the main canistersurface. At least one channel is located in the bottom of the insert 23to act as a conduit for fluid from the reservoir 10 to enter the base ofthe insert. The insert 23 includes fluid channels 14 that mate with theair exit ports 12 of the main canister 22. Peaks or extensions on theair exits 12 ensure centering of the insert 23 on the air exits. Asshown, fluid channels 14 of the insert 23 comprise two tubes with oneend at the bottom of the reservoir 10 and one end that is positioned inthe airstream so that the airstream creates a negative pressure in eachtube that draws fluid into the airstream where it is atomized (describedbelow).

In the embodiment shown in FIG. 1, the atomizer outlets 12, 14 extendabove the edge of the main canister 22. However, in an alternateembodiment (not shown) the atomizer nozzles are even with the edge ofthe main canister.

The insert 23 is keyed in at least one location with the reservoir 10 toensure that the insert does not rotate in relation to the exit ports 12of the main canister. The insert may include a feature to ensure that itis inserted into the main canister in only one orientation. In oneembodiment, a loop (not shown) extends down to the saddle of the insert23 to hold down the insert.

The fluid channels 14 are slightly larger in diameter than the air exitports 12 of the main canister, thereby providing a small space(preferably 0.0001″ to 0.010″ (0.00254-0.254 mm)) between the outersurface of the air exit ports and the inner surface of the fluidchannels. This space allows fluid from the reservoir 10 to proceedupward between the air exit ports 12 and the fluid channels 14 untilbeing expelled by pressurized air. When the insert 23 is installed inthe main canister 22, the orifices of the fluid channels 14 arepositioned relative to the air exits 12 so as to create a venturi effectwith the pressurized gas expelled from the gas tubes. Because the fluidexits 14 in the insert 23 are larger than the air exits 12, when air isforced through the air exits at an appropriate volume and speed, fluidin the reservoir 10 is drawn up into the space between the insert andair exits ports. When this fluid meets the subsequent airstream it isatomized into particles conducive to deposition in the upper airway. Theairstream is sufficient to penetrate the nasal cavity above the inferiorturbinate so as to deposit the fluid and provide a washing or irrigationto the upper reaches the nasal cavity.

The exit holes of the fluid channels 14 are small enough to ensure thatmist is created but large enough to ensure that the holes of the insertmay be chamfered so that the walls of the exit holes are angled awayfrom a central axis at an angle that exceeds the cone of the aerosolplume to reduce agglomeration of the mist particles upon exit, providinga more uniform particle size throughout the plume. The fluid channelsize may be adjusted to change the particle size of the mist. In oneembodiment the tubes have a mating section on the upper end that enablesthe changing of the orifice in the air stream via a series of nozzlesthat can be inserted into the upper end of the tubes such that the sizeof the nozzle orifice that is placed into the airstream is varied.

The third major section of the nebulizer is nozzle cone 3. The nozzle 3includes an air inlet 6 and a mating surface 7, which attaches to theair inlet 8 of the main canister 22 to create air chamber 11 defined bythe nozzle and the two exit ports 12 described above. The length of allcomponents on the nozzle cone 3 preferably is limited so that the nozzlecone or its components do not extend past the foot section 9 on the maincanister 22 when the device is assembled to enable the device to beplaced on a flat surface in an upright or standing position.

Ribs may also be molded into the nozzle cone 3 to provide radialstiffness. In another embodiment, the nozzle cone is made of rigidplastic.

The mating surface between the nozzle 3 and main canister 22 is designedto ensure a tight bond can be created. In an alternate embodiment themating surface between the nozzle 3 and main canister 22 is essentiallystraight.

In one embodiment, the nozzle cone 3 is attached permanently to the maincanister 22. In an alternate embodiment, the nozzle cone 3 may utilize afriction fit or have a positive connection such as a thread or othermechanism allowing the nozzle cone and main canister 22 to bedisconnected for cleaning. This detachable embodiment may include an airseal such as an O-ring as well as a flange to grasp for easydisassembly.

An air supply tube 5 connects the air inlet 6 of the nozzle cone with anair supply 17.

FIG. 2 shows a cross section view of the canister in accordance with analternate embodiment of the invention. In this embodiment, rather than asingle air chamber and nozzle, the canister 222 includes separate airpassage chambers 211 that terminate in the air exits 212. These separateair passage chambers 211 can connect to separate air sources viaseparate nozzles. Alternatively, the separate air passage chambers 211can be connected to a common air source via split tubing such as a Y orT adapter (not shown).

In addition to the three major sections described above, the nebulizermay include a cover 4 which has a mating surface 15 that creates anisodiametric connection to the main canister 22. In the example shown inFIG. 1, the cover 4 is a broad cover region to block space between thenose, eyes and the rest of the face when in use as shown (see FIG. 4).In this embodiment the cover 4 is designed to confine the mist expelledfrom the fluid channels and shield the patient's eyes, with an openingto provide room for the patient's nose within the apparatus. The cover 4is radiused along the distal end away from the main canister 22 to fit abroad variety of faces and is open to enable air to enter as the fluidis drawn down and capture and recycle fluid that falls off the face.

The cover may also incorporate a cross member or other device thatretains the insert 23 to allow for clearance of the nose and preventlifting of the insert at the initiation of atomization. In oneembodiment a sleeve or partial sleeve extends from the cover 4 to thebase of the insert 23 to hold the insert down.

FIG. 3 shows an alternate embodiment of the cover in accordance with thepresent invention. In this embodiment, the cover 304 is a semi-circularlid that does not block the eyes but instead retains the insert andblocks material from re-entering the main canister from the nose.

The present invention may incorporate a feature that guides the user toangle the spray into the nose at a set angle from 0-90 degrees from theplane defined as the front of the face from the chin to the forehead(i.e. the vertical plane of the face). For example, the nebulizer mayinclude a setoff designed to set a specific angle of 30 degrees, 45degrees, or 60 degrees from the vertical plane of the face. The setoffmay be removable for various size faces or noses.

Materials suitable for construction of the nebulizer include rigidplastic, glass, metal, ceramic, carbon fiber or other rigid material, oran elastomer plastic or some combination thereof.

One embodiment of the nasal irrigation device (not shown) is egg-shapedor ovoid for better fit into the hand and a pleasing look.

FIG. 4 illustrates the use of the nasal nebulizer in accordance with thepresent invention. The nebulizer is placed over the face of the user 18and angled such that the cover 4 blocks the eyes. The mist 20 enters thenasal passages 21, and the patient breathes through both the mouth andnose at the same time (22). The mist 20 passes into the nasal passages21 independent of the patient's breathing.

The air-fluid mixture is calibrated to achieve nasal irrigation within ashort period of time, without the need for the fluid to exit thenostrils at the time of irrigation, and with a particle size that isdesigned to loosen the mucous or to enter the sinus cavities, as desiredby the end user and not enter the pharynx or the lungs.

The method of nasal irrigation offers a fast, convenient method ofatomizing saline or medication for delivery to the nose, with a variableparticle size up to 100 microns. In one embodiment, particle size is atleast 10 microns.

Using an air pressure of 1-15 psi (0.069-1.035 bar) creates apressurized airflow that enables the resultant air-mist stream to stentopen the soft tissues of the upper airway. Optimal performance appearsto occur at 3-12 psi (0.207-0.823 bar), 1-12 lpm of airflow, and a fluiddelivery rate of 10-20 ml per minute but will vary according to theneeds of the patient. Typical performance is 4-8 psi (0.276-0.552 bar)pressure, 6-8 lmp airflow, and 15 ml per minute fluid delivery.

The resultant mist reaches the area of the nasal cavity above theinferior nasal turbinate or chonchae to ensure that the mist reaches theareas of the sinus ostia to clear this area of the nasal cavity andenable the natural mucociliary flow to clear the sinuses.

Recent medical research has noted that the olfactory and trigeminalnerves may be used as a pathway to deliver large and small molecules tothe brain and central nervous system that bypasses the blood brainbarrier and first pass metabolism of intravenous and oral deliveryroutes. (See Dhanda, D., Frey W H 2^(nd), Leopold, D., Kompella, U B:“Nose-to-brain delivery approaches for drug deposition in the humanolfactory epithelium.” Drug Delivery Technol. 5(4), 64-72 (2005).) Freyand others have demonstrated that these nerves may be reached via thenasal mucosa overlying the olfactory cleft and cribiform plate wherethese nerves are concentrated. Furthermore, the frequency of dosing ofmany of these materials requires a delivery system that is practical andeasy to use.

However, the literature suggests that adequate delivery systems arelacking for the reliable and practical delivery of these substances tothese areas. Delivery of large particles (>10 microns) of liquids insmall volumes, such as provided by the present invention, offersadvantages over dry powder and high volume solutions. These advantagesinclude the ability of the liquid to be formulated in such a way as toenable it to remain on the mucosa longer, such as thickening to a gel atbody temperature; reducing the inadvertent delivery of aerosolizedmaterials to the lungs; and the ability to deliver precious materialseconomically and judiciously while reducing waste.

The present invention provides a method for delivering steroids for thelong-term control of benign neoplasms of the nasal cavity, such asinflammatory nasal polyps, granulomas, etc., without systemic doses ofsteroids or steroid injections. It also provides the ability to irrigatethe whole nasal mucosa to manage the disruption of natural filtering andhumidification often caused by ablative and reconstructive surgicaltreatment of neoplasms. Unlike prior art saline irrigation and nasalsprays which do not reach many of the areas of concern in the nasalvestibule and paranasal sinus areas, the nebulizer of the presentinvention delivers adequate moisture in less than one minute to theareas of concern. The present invention also avoids pooling of moisturethat can otherwise provide a nidus for infection and cause excessiveremoval of the immunologic mucus blanket of the nose.

The high frequency of steroid administration needed to control neoplasmgrowth requires a delivery system that is practical and easy to use. Thenebulizer of the present invention can deliver these steroids quickly—inless than one minute—covering the whole nasal cavity and does so withoutunduly exposing the body to the effects of systemic steroids.

For example, using the nebulizer of the present invention, 60 mgs ofcorticosteroid is typically delivered to the nasal cavity, between threeand ten times the amount delivered via metered dose inhalers. In someinstances, antibiotics are delivered along with the corticosteroid totreat infections of Staphylococcus aureus. Staph Aureus endotoxin hasbeen shown to up-regulate the beta isoform of cortisol receptor (CR_(β))in cell membranes that is responsible for inhibiting the response tocorticosteroids, and it is believed that the Staph infection maycontribute to steroid-resistant nasal polyps. The concurrentadministration of antibiotics with the corticosteroid via the nebulizerof the present invention reduces this endotoxin effect on the cortisolreceptor, thereby increasing the efficacy of the steroid therapy.

The description of the present invention has been presented for purposesof illustration and description, and is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the art. Theembodiment was chosen and described in order to best explain theprinciples of the invention, the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated. It will be understood by one of ordinaryskill in the art that numerous variations will be possible to thedisclosed embodiments without going outside the scope of the inventionas disclosed in the claims.

We claim:
 1. A method of treating neoplasms of the nasal cavity,comprising: (a) providing fluid in a canister, wherein the canisterincludes a reservoir and at least two air exit ports and an insert, saidinsert comprising a base that fits within the canister; and wherein saidfluid contains corticosteroids; (b) mating said air exit ports tocorresponding fluid channels, wherein the fluid channels comprise twotubes ending in a common bell housing above the base of the insert andwherein the fluid channels are larger in diameter than the air exitports, thereby providing a space between the outer surface of the airexit ports and the inner surface of the fluid channels that allows fluidfrom said reservoir to be drawn upward between the air exit ports andfluid channels; and (c) pumping pressurized air through said air exitports, thereby creating a venturi effect that draws fluid from saidreservoir upward between the air exit ports and fluid channels andexpels the fluid as a mist in an aerosol plume through exit holes in thefluid channels and into a user's nasal cavity above the inferior nasalturbinate independent of the user's breathing, said mist comprising aparticle size of up to 100 microns and covering the whole nasal cavitywithin one minute; wherein said pressurized air has a pressure of0.069-1.035 bar and an airflow rate of 1-12 liters per minute, producinga fluid delivery rate of 10-20 ml per minute.
 2. The method according toclaim 1, wherein said fluid contains antibiotics.
 3. The methodaccording to claim 1, wherein the mist delivers up to 60 mg ofcorticosteroids to the nasal cavity within one minute.
 4. The methodaccording to claim 1, wherein said pressurized air has a pressure of0.276-0.552 bar.
 5. The method according to claim 1, wherein saidpressurized air has an airflow rate of 6-8 liters per minute.
 6. Themethod according to claim 1, wherein the fluid delivery rate is 15 mlper minute.
 7. The method according to claim 1, wherein the particlesize is at least 10 microns.